Eltrombopag-Induced Acute Liver Failure in a Pediatric Patient: A Pharmacokinetic and Pharmacogenetic Analysis

Abstract

Eltrombopag is an oral thrombopoietin receptor agonist approved for the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP), who are more than 1 year old, and show poor response to first-line therapy. ITP is a hematological disorder characterized by isolated thrombocytopenia in the absence of secondary causes or disorders. Eltrombopag is generally well tolerated in the pediatric population; therefore, therapeutic drug monitoring (TDM) is not usually performed in clinical practice.We presented the case study of a 3-year-old girl with chronic ITP. She arrived in the pediatric intensive care unit with acute liver failure due to eltrombopag toxicity despite taking the standard drug dosage. A very high eltrombopag plasma concentration, indicating drug toxicity, was found through TDM. The patient also carried the allelic variations that are involved in drug metabolism [CYP2C8 and UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1)] and drug cellular transportation [ABCG2 (ATP-binding cassette G2)]. This observation highlights the importance of using TDM and pharmacogenetic approaches to manage patients' unusual complications associated with standard pharmacological treatment regimens.

Eltrombopag-induced liver dysfunction during the treatment of immune thrombocytopenia and its risk factors

“…This may be due to the short timeframe of this study, because we only analyzed inpatient data, not follow-up data. It was reported that a 3-year-old patient with chronic ITP developed acute liver failure due to eltrombopag toxicity (15). A very high eltrombopag plasma concentration was found despite taking the standard drug dosage，and allelic variations that are involved in drug metabolism [CYP2C8 and UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1)] were carried in this patient.…”

Eltrombopag-induced Metabolic Acidosis and Hepatic Encephalopathy in Pediatric ITP

“…Interestingly, this patient demonstrated absence of elevated transaminases until well after hepatic and neurological symptoms developed. Notably, Marano et al8 reported a similar case involving a 3-year-old child suffering from chronic ITP with CYP2C8 variants who developed hepatic and neurological sequelae as a result of eltrombopag toxicity.…”

Immune thrombocytopenia in two infant cases managed with eltrombopag

“…Conversely, rebound thrombocytopenia is a known risk of abrupt TPO-RAs discontinuation. 10,11 However, because of the relatively recent wide use of this molecule, possible long-term effects of TPO-RAs are still unknown; this is particularly concerning when treating very young children.…”